Coronavirus disease 2019

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by SARS-CoV-2,[3] a virus closely related to the SARS virus.[4][5][6] The disease is the cause of the 2019–20 coronavirus outbreak.[7][8] It is primarily spread between people via respiratory droplets from infected individuals when they cough or sneeze.[9] Time from exposure to onset of symptoms is generally between 2 and 14 days.[10] Spread can be limited by handwashing and other hygiene measures.[11][12]

Coronavirus disease 2019
(COVID-19)
Other names
  • 2019-nCoV acute respiratory disease
  • Novel coronavirus pneumonia[1]
Symptoms of 2019 novel coronavirus (cropped).png
Symptoms
SpecialtyInfectious disease
SymptomsFever, cough, shortness of breath[2]
ComplicationsPneumonia, ARDS, kidney failure
CausesSARS-CoV-2
Diagnostic methodPCR testing, medical imaging
TreatmentSymptomatic and supportive

People may have few symptoms or develop fever, cough, and shortness of breath.[13][14][2] Cases can progress to pneumonia and multi-organ failure.[7][8] The mortality rate is around 2%.[15] There is no vaccine or specific antiviral treatment, with management involving treatment of symptoms, supportive care, and experimental measures.[16]

Cases were initially identified in Wuhan, capital of Hubei province in China in December 2019. Cases reported outside China have predominantly been in people who have recently travelled to Mainland China, however a few cases of local transmission have also occurred. More than 2,300 deaths have been reported in Mainland China, and 15 deaths in other parts of the world.[17]

The World Health Organization (WHO) and U.S. Centers for Disease Control (CDC) recommend that persons who suspect that they are carrying the virus wear a surgical face mask and seek medical advice by calling a doctor rather than directly visiting a clinic in person.[18][19] The WHO has declared the 2019–20 coronavirus outbreak to be a Public Health Emergency of International Concern (PHEIC).[20][21] As of 19 February 2020, only Mainland China was listed as an area with known ongoing community spread of the disease.[22]

Signs and symptoms

Those infected may either be asymptomatic or develop symptoms, including fever, cough or shortness of breath.[13][14][2] Diarrhea or upper respiratory symptoms (e.g. sneezing, runny nose, sore throat) are less frequent.[23] Cases can progress to pneumonia, multi-organ failure, and death.[7][8]

The length of the incubation period is estimated to be between two and ten days by the World Health Organization and between two and 14 days by the United States Centers for Disease Control and Prevention (CDC).[24][2] A study had found rare cases where the incubation period was as long as 24 days.[25]

Cause

 
Scanning electron microscope image of SARS-CoV-2 (yellow)

The disease is caused by the virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), previously referred to as the 2019 novel coronavirus (2019-nCoV).[5] The virus is thought to have an animal origin.[26]

It is primarily spread between people via respiratory droplets from the coughs and sneezes.[9] Officials in Shanghai confirmed several transmission modes, including direct transmission, contact transmission and aerosol transmission, the latter two involving transmission when someone touches a surface contaminated with tainted respiratory droplets and inhalation of air contaminated with tainted respiratory droplets.[27]

An epidemiological study of the first 72,314 cases suggested that there may have been a "continuous common source" of the outbreak in December 2019, which would imply that several animal to human zoonotic events occurred at the Huanan Seafood Wholesale Market. According to this theory, the primary source of infection became human-to-human transmission in early January 2020.[28]

Diagnosis

 
CDC laboratory test kit for COVID-19[29]

The WHO has published several testing protocols for the disease.[30][31] Testing uses real time reverse transcription-polymerase chain reaction (rRT-PCR).[32] The test can be done on respiratory or blood samples.[33] Results are generally available within a few hours to days.[34][35] Chinese scientists were able to isolate a strain of the coronavirus and publish the genetic sequence so that laboratories across the world could independently develop PCR tests to detect infection by the virus.[7][36][37][38][39]

Diagnostic guidelines released by Zhongnan Hospital of Wuhan University suggested methods for detecting infections based upon clinical features and epidemiological risk. These involved identifying patients who had at least two of the following symptoms in addition to a history of travel to Wuhan or contact with other infected patients: fever, imaging features of pneumonia, normal or reduced white blood cell count, or reduced lymphocyte count.[40]

Prevention

Global health organisations have published preventive measures to reduce the chances of infection. Recommendations are similar to those published for other coronaviruses: frequent washing of hands with soap and water; not touching the eyes, nose, or mouth with unwashed hands; and practicing good respiratory hygiene.[41][42]

The use of masks by healthy members of the public is not recommended outside of China.[43][11][12]

To prevent transmission, the CDC recommends that infected individuals stay at home except to get medical care; call ahead before visiting a healthcare provider; wear a facemask (especially in public); cover coughs and sneezes with a tissue; regularly wash hands with soap and water; and avoid sharing personal household items.[44]

No vaccine currently exists against SARS-CoV-2.

Management

There are no specific antiviral medications approved for this disease. Symptoms are managed with supportive care.[45] The WHO has published detailed treatment recommendations for hospitalized patients with severe acute respiratory infection (SARI) when a SARS-CoV-2 infection is suspected.[46] The WHO also recommended volunteers take part in randomized controlled trials for testing the effectiveness and safety of potential treatments.[47]

The Beijing branch of China's National Health Commission suggested the use of lopinavir/ritonavir as part of treatment plans in the absence of an approved drug for this indication.[48] The lopinavir/ritonavir combination and interferon can now be claimed for via health insurance in some countries.[49]

Psychological

Infected individuals may experience distress from quarantine, travel restrictions, side effects of treatment, or fear of the infection itself. To address these concerns, the National Health Commission of China published a national guideline for psychological crisis intervention on 27 January 2020.[50][51]

Alternative medicine

Chinese health authorities recommend the use of traditional Chinese medicine (TCM) in addition to standard medical supportive care to prevent or treat the disease. On 22 January, National Health Commission put TCM into the third issue of the COVID diagnostic and treatment plan.[52] On 2 February, Wuhan officials ordered all patients to be put on a specific TCM treatment.[53][54] On 14 February, Wuhan opened a TCM-oriented temporary hospital.[55] The efficacy and safety of TCM has not been established in coronavirus infections.[56][57]

Prognosis

According to WHO, based on analysis of 44,000 cases of COVID-19 in Hubei province, around 80% of patients only have a mild form of the disease, 14% developed more severe disease such as pneumonia, 5% have critical disease, and 2% of cases are fatal.[15] Among those who died initially, many had preexisting conditions, including hypertension, diabetes, or cardiovascular disease,[58] and the median time from initial symptoms to death was 14 days (range 6-41 days).[59]

Epidemiology

Overall mortality and morbidity rates due to infection are not well established; while the case fatality rate changes over time in the current outbreak, the proportion of infections that progress to diagnosable disease remains unclear.[60][61] However, preliminary research has yielded case fatality rate numbers between 2% and 3%;[62] in January 2020 the WHO suggested that the case fatality rate was approximately 3%,[63] and 2% in February 2020 in Hubei.[64] An unreviewed preprint study by Imperial College London among 55 fatal cases noted that early estimates of mortality may be too high as asymptomatic infections are missed. They estimated a mean infection fatality ratio (the mortality among infected) ranging from 0.8% when including asymptomatic carriers to 18% when including only symptomatic cases from Hubei province.[65]

Research

Vaccine

Many organizations are using published genomes to develop possible vaccines against SARS-CoV-2.[66][67] Bodies developing vaccines include the Chinese Center for Disease Control and Prevention,[68][69] the University of Hong Kong,[70] and Shanghai East Hospital.[70] Three vaccine projects are being supported by the Coalition for Epidemic Preparedness Innovations (CEPI), including projects by the biotechnology companies Moderna and Inovio Pharmaceuticals and another by the University of Queensland.[71] The United States National Institutes of Health (NIH) is cooperating with Moderna to create an RNA vaccine matching a spike of the coronavirus surface, and intends to start human trials by May 2020.[66] Inovio Pharmaceuticals is developing a DNA-based vaccination and collaborating with a Chinese firm, hoping to perform human trials in the summer of 2020.[72] In Australia, the University of Queensland is investigating the potential of a molecular clamp vaccine that would genetically modify viral proteins in order to stimulate an immune reaction.[71] In Canada, the International Vaccine Centre (VIDO-InterVac), University of Saskatchewan, are working on a vaccine,[73] aiming to start animal testing in March 2020 and human testing in 2021.[73]

In January 2020, Janssen Pharmaceutical Companies began work on developing a vaccine, utilizing the same technologies used to make its experimental Ebola vaccine.[74] In the following month, the U.S. Department of Health and Human Services' Biomedical Advanced Research and Development Authority (BARDA) announced that it would collaborate with Janssen and, later, Sanofi Pasteur (the vaccine division of Sanofi) to develop a vaccine.[75][76] Sanofi has previously worked on a vaccine for SARS and it stated to expect to have a vaccine candidate within six months that could be ready to test in people within a year to 18 months.[75]

Antiviral

No drug has yet been approved to treat coronavirus infections in humans.[77] Research into potential treatments for the disease was initiated in January 2020, and several antiviral drugs are already in clinical trials.[66][67] Although completely new drugs may take until 2021 to develop,[78] several of the drugs being tested are already approved for other antiviral indications, or are already in advanced testing.[77]

Antivirals being tested include chloroquine;[79] darunavir;[80] galidesivir;[citation needed] interferon beta;[81][better source needed] the lopinavir/ritonavir combination;[82][67] PRO 140;[citation needed] REGN3048-3051 (Regeneron), a combination of two neutralizing monoclonal antibodies;[citation needed] the RNA polymerase inhibitor remdesivir;[83][84][81] and triazavirin.[85][better source needed]

Arbidol and Darunavir were proposed by the National Health Commission.[86][better source needed]

One multicentric trial has shown chloroquine to be effective and safe in COVID-19 associated pneumonia.[87]The drug is also being reported to be included in Guidelines for the Prevention, Diagnosis, and Treatment of Pneumonia Caused by COVID-19 issued by the National Health Commission of the People's Republic of China for treatment of COVID-19 infection in larger populations in the future.[87]

Terminology

The World Health Organization on 11 February 2020 announced that "COVID-19" will be the official name of the disease. World Health Organization chief Tedros Adhanom Ghebreyesus said "co" stands for "corona", "vi" for "virus" and "d" for "disease", while "19" was for the year, as the outbreak was first identified on December 31. Tedros said the name had been chosen to avoid references to a specific geographical location (i.e. China), animal species or group of people in line with international recommendations for naming aimed at preventing stigmatization.[88][89]

See also

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